MicroRNAs (miRNAs) are small noncoding RNAs that are known to participate in the regulation of many physiological and pathological processes, which can indirectly influence the development of malignant behaviors. Numerous studies have demonstrated that miR-449a plays important roles in human carcinogenesis. However, its precise functional and regulatory roles remain unclear. In this study, we mainly explored the functional role of miR-449a in gastric cancer (GC). The expression levels of miR-449a in 98 cases of GC tissues and cell lines were determined by qRT-PCR. The possible mechanisms of miR-449a in GC cells were explored by fluorescence reporter assay. miR-449a expression was significantly lower in GC tissues compared to matched para-carcinoma tissues and was associated with tumor differentiation. Furthermore, in vitro knockdown of miR-449a by siRNA significantly inhibited MKN-28 cell proliferation, migration and invasion as well as tumorigenesis via inducing G0/G1 arrest of GC cells. In addition, we identified SGPL1 as a target of miR-449a and demonstrated that miR-449a regulated SGPL1 expression via binding its 3′-UTR region. The experiments indicated that miR-449a functions as a novel tumor suppressor in GC and its anti-oncogenic activity may involve its inhibition of the target gene SGPL1. These findings suggested that miR-449a may be a promising candidate for the development of antitumor drugs targeting GC.

中文翻译：

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抑癌基因 miR-449a 通过下调 SGPL1 抑制胃癌的发展

MicroRNAs (miRNAs) 是已知参与调控许多生理和病理过程的小型非编码 RNA，可间接影响恶性行为的发展。大量研究表明，miR-449a 在人类致癌过程中起重要作用。然而，其确切的功能和监管作用仍不清楚。在本研究中，我们主要探讨了 miR-449a 在胃癌 (GC) 中的功能作用。通过qRT-PCR测定98例GC组织和细胞系中miR-449a的表达水平。通过荧光报告基因分析探讨了 miR-449a 在 GC 细胞中的可能机制。与匹配的癌旁组织相比，miR-449a 在 GC 组织中的表达显着降低，并且与肿瘤分化有关。此外，体外siRNA 敲低 miR-449a通过诱导 GC 细胞 G0/G1 期阻滞显着抑制 MKN-28 细胞增殖、迁移和侵袭以及肿瘤发生。此外，我们将 SGPL1 鉴定为 miR-449a 的靶标，并证明 miR-449a通过结合其 3'-UTR 区域来调节 SGPL1 的表达。实验表明 miR-449a 在 GC 中作为一种新型肿瘤抑制因子发挥作用，其抗癌活性可能涉及其对靶基因 SGPL1 的抑制。这些发现表明 miR-449a 可能是开发靶向 GC 的抗肿瘤药物的有希望的候选者。